ABSTRACT
17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.
Subject(s)
Central Nervous System Diseases , Dental Enamel/abnormalities , Diabetes Mellitus, Type 2 , Kidney Diseases, Cystic , Male , Humans , Adult , Japan , Face , HeterozygoteABSTRACT
Purpose: To investigate the effect of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) on connective tissue growth factor (CTGF) expression in adult retinal pigment epithelial (ARPE)-19 cells. We also studied the inhibitory effect of K-975, a new pan-transcriptional enhanced associate domain (TEAD) inhibitor, and luteolin, a plant-derived flavonoid on CTGF expression. Methods: ARPE-19 cells were transfected with either YAP or TAZ overexpression plasmid or treated with transforming growth factor (TGF)-ß2. The cells were cultured either with or without K-975 or luteolin. The expression of YAP, TAZ, and CTGF was examined using real-time PCR. Results: ARPE-19 cells overexpressing YAP or TAZ exhibited significantly increased CTGF expression. This increase was attenuated by K-975 or luteolin alone. TGF-ß2 treatment significantly raised the expression of not just YAP and TAZ, but also CTGF in ARPE-19 cells. TGF-ß2 treatment-enhanced CTGF expression was considerably lowered by the addition of K-975 or luteolin. Conclusions: Overexpression of YAP or TAZ and treatment with TGF-ß2 led to an increase in the expression of CTGF in ARPE-19 cells. These increases were attenuated by treatment with K-975 and luteolin. These findings suggest that YAP and TAZ may be related to the expression of CTGF in ARPE-19 cells and that K-975 and luteolin can be explored as potential therapeutic agents for preventing CTGF production in vitreoretinal fibrosis.
Subject(s)
Connective Tissue Growth Factor , Luteolin , Retinal Pigment Epithelium , Transcription Factors , Connective Tissue Growth Factor/metabolism , Humans , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/cytology , Luteolin/pharmacology , Transcription Factors/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Cell Line , Trans-Activators/metabolism , Transforming Growth Factor beta2/metabolism , Transforming Growth Factor beta2/pharmacology , Transforming Growth Factor beta2/antagonists & inhibitors , YAP-Signaling Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/geneticsABSTRACT
PURPOSE: We investigated whether heat-shock transcription factor 1 (HSF1) was involved in ultraviolet radiation type B (UVR-B)-induced lens opacity (cataract) using HSF1 heterozygous mice. We also examined the effects of geranylgeranylacetone (GGA), an inducer of heat-shock proteins via activation of HSF, on the UVR-B-induced cataract. MATERIAL AND METHODS: Male HSF1+/- and WT mice were unilaterally exposed to UVR-B (total: 1200mJ) at 16 weeks of age. At 48 h after the last UVR-B irradiation, the lens was isolated and the induction of the cataract was quantified as the cataract area ratio (opacity area/anterior capsule). GGA was orally administered at a dosage of 500 mg/kg once a day for two days before the first UVR-B exposure until the end of the experiment (21days in total). RESULTS: The HSF1 expression was more greatly decreased in the lens from HSF1+/- mice than in that from WT mice (p < 0.01). UVR-B exposure could mainly induce cataracts in the anterior capsule in both HSF1+/- and WT mice, while the opacity of the lens was markedly enhanced in HSF1+/- mice compared to that in WT mice(p (0.01). GGA treatment could prevent the induction of lens opacity by UVR-B exposure in both WT and HSF1+/- mice as compared with the non-administration group (p < 0.01). No obvious alteration by the UVR-B radiation was seen in lens protein levels of αA-crystallin, αB-crystallin, or γ-crystallin with or without GGA administration among all groups of mice. In contrast to the crystallins, the lens protein level of HSP25 was decreased by UVR-B exposure in both HSF1+/- and WT mice, and was significantly recovered in WT mice by the GGA treatment (p < 0.01). The induction of HSP25 was suppressed in HSF1+/- mice compared with that in WT mice. CONCLUSIONS: These data suggest that HSF1 plays an important role in the occurrence of UVR-B-induced cataracts, possibly via regulation of HSPs such as HSP25.
Subject(s)
Cataract/drug therapy , Diterpenes/pharmacology , Gene Expression Regulation , Heat Shock Transcription Factors/genetics , Lens, Crystalline/metabolism , RNA/genetics , Radiation Injuries, Experimental , Animals , Blotting, Western , Cataract/etiology , Cataract/metabolism , DNA Mutational Analysis , Dose-Response Relationship, Radiation , Female , Heat Shock Transcription Factors/biosynthesis , Heterozygote , Lens, Crystalline/pathology , Lens, Crystalline/radiation effects , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Real-Time Polymerase Chain Reaction , Transcription Factors , Ultraviolet Rays/adverse effectsABSTRACT
PURPOSE: To determine the clinical significance of retinal pigment epithelium (RPE) undulations in the acute stage of Vogt-Koyanagi-Harada disease. METHODS: Retinal pigment epithelium undulations were detected and classified into 3 grades: Grade 1, slight; Grade 2, moderate; and Grade 3, severe undulations, in the enhanced depth imaging optical coherence tomographic images. The relationship between the clinical characteristics and the presence of RPE undulations was investigated. RESULTS: Among the 61 eyes of 31 patients with Vogt-Koyanagi-Harada disease, 40 eyes had some degree of RPE undulations (Grade 1 = 12, Grade 2 = 15, and Grade 3 = 13). The patients with RPE undulations in both eyes were significantly older at the onset (P = 0.0002). The eyes with RPE undulations were more likely to develop posterior recurrences (P = 0.032) and have worse vision at 12 months (P = 0.043). Multiple regression analysis revealed that RPE undulations were an independent predictor of posterior recurrences (P = 0.009) and poor visual outcomes (P = 0.035). CONCLUSION: Retinal pigment epithelium undulations detected by enhanced depth imaging optical coherence tomographic are relatively frequent occurrences at the acute stage of Vogt-Koyanagi-Harada, and their presence is a predictor of posterior recurrences and poor visual outcomes after high-dose steroid therapy.
Subject(s)
Biomarkers , Glucocorticoids/administration & dosage , Retinal Detachment/diagnosis , Retinal Pigment Epithelium/pathology , Uveomeningoencephalitic Syndrome/diagnosis , Acute Disease , Administration, Oral , Adult , Aged , Betamethasone/administration & dosage , Drug Combinations , Female , Fluorescein Angiography , Humans , Infusions, Intravenous , Male , Methylprednisolone/administration & dosage , Middle Aged , Prednisolone/administration & dosage , Retinal Detachment/classification , Retinal Detachment/drug therapy , Tomography, Optical Coherence , Uveomeningoencephalitic Syndrome/classification , Uveomeningoencephalitic Syndrome/drug therapy , Visual Acuity/physiologyABSTRACT
PURPOSE: To assess the 1-year outcome of half-dose verteporfin photodynamic therapy (PDT) for patients with chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, interventional case series with no controls. PARTICIPANTS: A total of 204 eyes of 204 patients with chronic CSC were studied. METHODS: Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed before PDT. The best-corrected visual acuities (BCVAs) were measured and optical coherence tomography was performed before and 1, 3, 6, 9, and 12 months after PDT. MAIN OUTCOME MEASURES: The main outcome measures were the resolution of the serous retinal detachment (SRD), changes in BCVA, and ocular and systemic complications at 12 months. RESULTS: A total of 182 of 204 eyes (89.2%) had complete resolution of the SRD at 12 months after the PDT. Eleven eyes (5.4%) had a persistent SRD throughout the follow-up period, and 12 eyes (5.9%) had a recurrence of the SRD after an earlier resolution. One of the 12 eyes had a spontaneous resolution of the SRD 6 months after PDT. The mean±standard deviation BCVA in logarithm of the minimum angle of resolution (logMAR) units significantly improved from 0.11±0.25 before to 0.07±0.23 at 1 month, 0.02±0.23 at 3 months, 0.01±0.23 at 6 months, 0.00±0.24 at 9 months, and -0.01±0.22 at 12 months (P<0.0001). The eyes with an SRD at 12 months were more likely to have an intermediate hyperfluorescence on ICGA (chi-square test, P<0.001) and poorer BCVA before the half-dose PDT (Student t test, P=0.04) than those without SRD at 12 months. None of the patients developed any systemic complications or experienced any severe visual reduction after the half-dose PDT. However, polypoidal lesion appeared in 1 eye 8 months after the PDT. CONCLUSIONS: Half-dose PDT is an effective and safe method to treat eyes with chronic CSC with an SRD. The CSC resolved and the BCVA improved significantly after PDT. Half-dose PDT was less effective for cases without intense hyperpermeability on ICGA and those with lower BCVA before the PDT.
Subject(s)
Central Serous Chorioretinopathy/drug therapy , Photochemotherapy , Photosensitizing Agents/administration & dosage , Porphyrins/administration & dosage , Adult , Aged , Aged, 80 and over , Central Serous Chorioretinopathy/physiopathology , Chronic Disease , Coloring Agents , Female , Fluorescein Angiography , Follow-Up Studies , Humans , Indocyanine Green , Male , Middle Aged , Retinal Detachment/physiopathology , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Verteporfin , Visual Acuity/physiologyABSTRACT
PURPOSE: To examine whether astaxanthin (AST) prevent the cataract formation induced by glucocorticoid in chick embryo. MATERIALS AND METHODS: Hydrocortisone hemisuccinate sodium (HC) (0.5 µmol/egg) was administered directly into the air chamber in the egg shell of chick embryo day 15. The eggs were then kept in an incubator at same conditions and administered 100 µL of 50 (HC + AST50 group), 80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC treated group (treated with physiological saline without HC and 100 µL of DMSO), HC-alone group (treated with 0.5 µmol of HC and 100 µL of DMSO), and AST100 group (treated with physiological saline without HC and 100 µL of DMSO) were also incorporated. After 48 h of treatment, lenses were removed from embryo and classified into five stages according to developed opacity. The amounts of reduced glutathione in the lenses and the blood glucose levels were measured. RESULTS: The average scores of lens opacitiy were 2.63 ± 1.02 nmol/lens (HC-alone), 2.78 ± 0.97 nmol/lens (HC + AST50), 2.22 ± 1.20 nmol/lens (HC + AST80) and 1.84 ± 0.83 nmol/lens (HC + AST100; p < 0.05), respectively. Administration of AST decreased the lens opacity dose-dependently. The amounts of reduced glutathione in lenses were 11.6 ± 2.8 nmol/lens (HC-alone), 11.3 ± 2.7 nmol/lens (HC + AST50), 13.4 ± 2.4 nmol/lens (HC + AST80) and 13.7 ± 3.1 nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented loss of reduced glutathione from the lens. CONCLUSION: These findings support that AST protects glucocorticoid-induced cataract in chick embryo.
Subject(s)
Cataract/prevention & control , Lens, Crystalline/drug effects , Animals , Cataract/chemically induced , Cataract/embryology , Chick Embryo , Disease Models, Animal , Fibrinolytic Agents/therapeutic use , Glucocorticoids/toxicity , Lens, Crystalline/embryology , Lens, Crystalline/metabolism , Oxidative Stress/drug effects , Xanthophylls/therapeutic useABSTRACT
PURPOSE: To determine the retinal structures affecting the recovery of macular function in patients with exudative age-related macular degeneration (AMD) treated with intravitreal ranibizumab (IVR). METHOD: Thirty eyes of 30 patients with exudative AMD who were treated with IVR at monthly intervals for 3 months were studied. Focal macular electroretinograms (fmERGs) and spectral-domain optical coherence tomography (SD-OCT) were performed before and 3 months after beginning the IVR injections. The fmERGs were elicited by a 15° white stimulus spot centered on the fovea. The thickness of different retinal layers, presence of a serous retinal detachment (SRD), and presence of a pigment epithelial detachment (PED) at the fovea was determined in the SD-OCT images. Measurements were made of the inner, middle, and outer layers of the retina and also of the SRD and PED in the horizontal and vertical meridians at 1.2 mm from the fovea (parafoveal regions). The significance of the correlations between these structural parameters and the a-wave amplitude of the fmERG was determined. RESULTS: There was no significant correlation between the structural parameters of the fovea and the a-wave amplitude. In the parafoveal regions, the thickness of the outer retinal layer was significantly correlated with an increase of the a-wave amplitude (R = 0.56, P = 0.001). In addition, the SRD thickness was negatively and significantly correlated with the a-wave amplitude (R = -0.54, P = 0.002). The change in the parafoveal SRD thickness after IVRs was the only independent determinant of recovery of the a-wave amplitude after the treatments (P < 0.05). CONCLUSIONS: The macular function measured by the fmERGs was determined by the parafoveal outer layer and SRD thickness in patients with exudative AMD. Of these, changes in the SRD thickness by IVRs most strongly affected the recovery of macular function.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Ranibizumab/therapeutic use , Recovery of Function/physiology , Retina/physiology , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/physiopathology , Aged , Aged, 80 and over , Electroretinography , Female , Humans , Intravitreal Injections , Male , Middle Aged , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiologyABSTRACT
Here we report a case of Churg-Strauss syndrome (CSS) and central retinal artery occlusion (CRAO), with good visual recovery. A 58-year-old Japanese man with CSS experienced acute painless loss of vision in his right eye. CRAO was diagnosed by fundoscopic findings (retinal whitening with a cherry-red spot). Steroid pulse therapy (methylprednisolone at 1 g daily for 3 days) followed by combined treatment with prednisolone (30 mg/day) and cyclophosphamide (150 mg/day) was administered; his visual acuity recovered to 20/30 in 1 month, and no recurrence has occurred for 1 year. Steroid pulse therapy may be effective for CRAO in CSS patients.
Subject(s)
Churg-Strauss Syndrome/complications , Cyclophosphamide/administration & dosage , Prednisolone/administration & dosage , Recovery of Function/drug effects , Retinal Artery Occlusion , Glucocorticoids/administration & dosage , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Pulse Therapy, Drug , Retinal Artery Occlusion/drug therapy , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/pathologyABSTRACT
We investigated whether decreased vitamin C (VC) in a mouse model increases lens opacity (cataract) induced by in vivo exposure to ultraviolet radiation type B (UVR-B). Senescence marker protein-30 (SMP30) knockout (KO) mice, which cannot synthesize VC due to genetic disruption of the gluconolactonase (GNL) gene, were divided into 2 groups: VC sufficient (VC (+)) and VC deficient (VC (-)). Starting at 1 month of age, these groups had free access to water containing 0.0375 and 1.5 g/L of VC, respectively. SMP30 KO VC (-), SMP30 KO VC (+), and wild-type (WT) mice, all 14 weeks of age, were unilaterally exposed in vivo to UVR-B (200 mW/cm(2)) for 100 s twice a week for 3 weeks (total: 1200 mJ/cm(2)). At 48 h after the last UVR-B exposure, cataract morphology was documented, and the ratio of cataract induction was quantified as the cataract area ratio (opacity area/anterior capsule). UVR-B exposure induced cataract mainly at anterior sub-capsular in SMP30 KO VC (-), SMP30 KO VC (+), and WT mice. In SMP30 KO VC (-) lenses the opacities were more extensive than in SMP30 KO VC (+) or WT lenses (cataract area ratios: 59.3% ± 10% vs. 32.2% ± 11.7% or 29.0% ± 9.0%; P < 0.01). In conclusion, VC depletion may increase the susceptibility to develop UVR-B induced cataracts in mice unable to endogenously produce VC.
Subject(s)
Ascorbic Acid Deficiency/complications , Ascorbic Acid/physiology , Cataract/etiology , Lens, Crystalline/radiation effects , Radiation Injuries, Experimental/etiology , Ultraviolet Rays/adverse effects , Animals , Ascorbic Acid Deficiency/metabolism , Calcium-Binding Proteins/genetics , Carboxylic Ester Hydrolases/genetics , Cataract/metabolism , Cataract/pathology , Disease Models, Animal , Intracellular Signaling Peptides and Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/pathologyABSTRACT
PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease presenting mutton fat like subretinal precipitates. DESIGN: Observational case report. METHODS: A 52-year-old Japanese woman developed bilateral uvetis with serous retinal detachment and mutton fat like subretinal precipitates. RESULTS: According to Opthalmologic, auditory, and systemic examination, we diagnosed the patient with VKH disease. Inflamation was controlled by three time steroid therapy and subretinal fluid and precipitates decreased and disappeared. CONCLUSIONS: Subretinal granulomatous lesion may present a manifestation of VKH and mean long standing subretinal fluid and inflammation.
Subject(s)
Retinal Detachment/diagnosis , Uveomeningoencephalitic Syndrome/diagnosis , Female , Humans , Japan , Methylprednisolone/therapeutic use , Middle Aged , Retinal Detachment/drug therapy , Retinal Detachment/pathology , Treatment Outcome , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/pathology , Visual AcuityABSTRACT
BACKGROUND: We report a case of herpes simplex virus (HSV) epithelial keratitis that developed after a subtenon triamcinolone acetonide (TA) injection. METHOD: A 78-year-old woman with a branch retinal vein occlusion and diffuse macular edema in her left eye received a subtenon injection of 20 mg of TA. RESULTS: Six days after the injection, the patient presented with a foreign body sensation, tearing, redness, and photophobia in the same eye. Slit-lamp examination revealed multiple corneal dendriform ulcers. She was diagnosed with HSV epithelial keratitis and treated with topical acyclovir ointment. The epithelial lesions healed after 1 week of therapy. CONCLUSION: HSV epithelial keratitis can be a possible complication of a TA subtenon injection.
Subject(s)
Epithelium, Corneal/virology , Glucocorticoids/adverse effects , Herpesvirus 1, Human/physiology , Keratitis, Herpetic/etiology , Triamcinolone Acetonide/adverse effects , Acyclovir/therapeutic use , Aged , Antiviral Agents/therapeutic use , Fascia , Female , Humans , Injections , Keratitis, Herpetic/drug therapy , Macular Edema/drug therapy , Macular Edema/etiology , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/drug therapy , Virus Activation/drug effectsABSTRACT
The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1(-/-) mice. The amplitudes of the a- and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1(-/-) mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1(-/-) mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1(-/-) and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1(-/-) mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1(-/-) mice also present progressive retinal degeneration. Our results indicate that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration.
Subject(s)
Retina/pathology , Retina/physiopathology , Retinal Degeneration/pathology , Retinal Degeneration/physiopathology , Superoxide Dismutase/physiology , Aging , Animals , Apoptosis , Caspase 3/physiology , Cell Nucleus/metabolism , Cell Nucleus/pathology , Crosses, Genetic , Electroretinography , Mice , Mice, Inbred C57BL , Mice, Knockout , Necrosis , Retina/metabolism , Retinal Degeneration/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase-1ABSTRACT
A 41-day-old female infant with VACTERL association was transferred to the pediatric intensive care unit of our hospital. She had been delivered at 36 weeks gestation by spontaneous vaginal delivery and weighed 2340 g. Esophageal atresia type A with long gap, anal atresia, cardiac anomaly (atrial septal defect and patent ductus arteriosus), thoracic vertebral dysplasia, left renal agenesis, and minor anomalies (left-side facial nerve palsy, left-side difficulty in hearing, and the absence of the right thenar) had been diagnosed by various examinations. She was transferred to our hospital to receive treatment for heart failure due to a cardiac anomaly. We recognized vaginal atresia during a radical operation for anal atresia (rectovestibular fistula) at 8 months of age. Furthermore, magnetic resonance imaging (MRI) revealed agenesis of the uterus. MURCS association includes Mullerian duct aplasia or hypoplasia, renal aplasia, and cervicothoracic somite dysplasia. This is the first case of complete VACTERL association combined with MURCS association.
Subject(s)
Abnormalities, Multiple/diagnosis , Anus, Imperforate/diagnosis , Bone Diseases, Developmental/diagnosis , Vagina/abnormalities , Abnormalities, Multiple/surgery , Anus, Imperforate/surgery , Bone Diseases, Developmental/surgery , Female , Humans , Infant , Magnetic Resonance Imaging , Respiratory InsufficiencyABSTRACT
Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1(-/-) mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1(-/-) mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1(-/-) mice showed oxidative damage, and their beta-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1(-/-) mouse is a valuable animal model to study human age-related macular degeneration.
Subject(s)
Choroid Diseases/pathology , Macular Degeneration/genetics , Macular Degeneration/pathology , Neovascularization, Pathologic , Optic Disk Drusen/pathology , Pigment Epithelium of Eye/metabolism , Superoxide Dismutase/genetics , Animals , Choroid Diseases/genetics , Disease Models, Animal , Light , Mice , Mice, Inbred C57BL , Mice, Transgenic , Optic Disk Drusen/genetics , Oxidative Stress , Superoxide Dismutase-1 , beta Catenin/metabolismABSTRACT
We isolated and characterized the Xenopus translocon-associated protein XTRAP-gamma, one of four subunits of the translocon-associated protein complex. TRAP has been proposed to aid the translocation of nascent polypeptides into the lumen of the endoplasmic reticulum, but this has not been demonstrated until now. XTRAP-gamma was specifically expressed in the pronephros tubules of Xenopus laevis from stage 25 during kidney development. Antisense morpholino oligonucleotide-mediated knockdown of XTRAP-gamma suppressed tubulogenesis and decreased expression of the pronephros marker genes Pax-2 and Wnt-4. XTRAP-gamma morpholinos also inhibited differentiation of the pronephros in activin/retinoic acid-treated animal caps. We conclude that XTRAP-gamma plays an important role in the process of pronephros differentiation.
Subject(s)
Calcium-Binding Proteins/physiology , Embryo, Nonmammalian/physiology , Kidney/embryology , Membrane Glycoproteins/physiology , Receptors, Cytoplasmic and Nuclear/physiology , Receptors, Peptide/physiology , Xenopus Proteins/physiology , Xenopus laevis/embryology , Activins/metabolism , Amino Acid Sequence , Animals , Calcium-Binding Proteins/chemistry , Calcium-Binding Proteins/genetics , Gene Expression Regulation, Developmental , Gene Library , Homeodomain Proteins , In Situ Hybridization , Inhibins , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/genetics , Molecular Sequence Data , Oligonucleotides, Antisense , Receptors, Cytoplasmic and Nuclear/chemistry , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Peptide/chemistry , Receptors, Peptide/genetics , Up-Regulation , Xenopus Proteins/geneticsABSTRACT
PURPOSE: The local renin-angiotensin system (RAS) is present in the ciliary body and plays a role in regulating aqueous humor dynamics and thus intraocular pressure (IOP). The purpose of this study was to determine whether gene polymorphisms in the RAS increase the risk of development of glaucoma in the Japanese. METHODS: A case-control study was performed in 698 Japanese subjects: 190 patients with primary open-angle glaucoma (POAG), 268 patients with normal-tension glaucoma (NTG), and 240 normal subjects. Ten polymorphisms in seven genes-AGT/Thr174Met and AGT/Met235Thr; REN/I8-83G-->A; ACE/insertion(I)-deletion(D); CMA/-1930A-->G; AGTR1/-731T-->G, AGTR1/-521C-->T, and AGTR1/1166A-->C; AGTR2/3123C-->A; and CYP11B2/-344T-->C were examined. The age, IOP, and visual field defects, all at diagnosis, were examined to determine whether they were associated with the polymorphisms. The effects of oral angiotensin II receptor blocker (ARB) on IOP were examined in association with the AGTR1 and AGTR2 polymorphisms in 20 normal subjects. RESULTS: Of the 10 polymorphisms, the AGTR2/3123C-->A polymorphisms had a significantly different distribution in female patients with NTG; the frequency of the CA+AA genotypes was significantly higher than in female control subjects (P = 0.0095 for CC versus CA+AA). Although no significant difference was seen in the clinical characteristics of female patients with NTG who carried the AGTR2/3123C-->A genotype, patients with CC in the AGTR2 gene had significantly worse visual field scores if they carried ACE/ID+DD (i.e., D carriers; P = 0.012). ARB significantly lowered IOP in normal subjects, but the male subjects with the AGTR2/3123A genotype had significantly less lowering of IOP than those with the C genotype (P = 0.014). CONCLUSIONS: Angiotensin II receptor gene polymorphisms may be associated with the risk of glaucoma in the Japanese population.